Is transformed small cell lung cancer (SCLC) different from de novo SCLC?

Small cell lung cancer (SCLC) transformation is one of the mechanisms for acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC) (1-5). Although two types of histology are commonly thought to be different diseases, Oser et al. suggested that both combined histology tumors and SCLC transformation are possible because the type II alveolar cells, which are the cells of origin of some EGFR-mutant adenocarcinomas (ADC), may be transformed into SCLC (1). SCLC transformation from ADC has been sometimes observed in EGFR-wild type lung cancers that lack other mutations (6,7) or during anaplastic lymphoma kinase (ALK)-targeted therapy (8-10) and programed cell death-1 (PD-1) immunotherapy (11,12). In addition, SCLC transformation has sometimes been reported in cancers other than lung cancer probably as a result of frequent repeat biopsies (13,14).